期刊
CELL AND TISSUE RESEARCH
卷 383, 期 1, 页码 495-506出版社
SPRINGER
DOI: 10.1007/s00441-020-03402-7
关键词
GABA; Granule cells; Olfactory processing
类别
资金
- Projekt DEAL
- Integrative Analysis of Olfaction [SPP 1392]
- BMBF [FKZ 01GQ1104/1502]
Recent research has shed light on the mechanisms of GABA release from the reciprocal spine of granule cells, demonstrating the necessity of a local spine action potential and the cooperative action of NMDA receptors and high voltage-activated Ca2+ channels. This supports the notion that lateral inhibition is dependent on the activity of principal neurons connected to granule cells and is closely related to recurrent inhibition, providing directed, dynamically switched lateral inhibition in a sensory system with 1000 input channels organized in glomerular columns. The mechanistic underpinnings of this hypothesis are supported by findings from odor discrimination behavior in mice with synaptic proteins deleted in granule cells, explaining the unique microcircuit of granule cell reciprocal spines as a means of olfactory combinatorial coding.
The role of granule cells in olfactory processing is surrounded by several enigmatic observations, such as the purpose of reciprocal spines and the mechanisms for GABA release, the apparently low firing activity and recurrent inhibitory drive of granule cells, the missing proof for functional reciprocal connectivity, and the apparently negligible contribution to lateral inhibition. Here, we summarize recent results with regard to both the mechanisms of GABA release and the behavioral relevance of granule cell activity during odor discrimination. We outline a novel hypothesis that has the potential to resolve most of these enigmas and allows further predictions on the function of granule cells in odor processing. Briefly, recent findings imply that GABA release from the reciprocal spine requires a local spine action potential and the cooperative action of NMDA receptors and high voltage-activated Ca2+ channels. Thus, lateral inhibition is conditional on activity in the principal neurons connected to a granule cell and tightly intertwined with recurrent inhibition. This notion allows us to infer that lateral inhibition between principal neurons occurs on demand, i.e., selectively on coactive mitral and tufted cells, and thus can provide directed, dynamically switched lateral inhibition in a sensory system with 1000 input channels organized in glomerular columns. The mechanistic underpinnings of this hypothesis concur with findings from odor discrimination behavior in mice with synaptic proteins deleted in granule cells. In summary, our hypothesis explains the unusual microcircuit of the granule cell reciprocal spine as a means of olfactory combinatorial coding.
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